Metals toxicity and its correlation with the gene expression in Alzheimer's disease

Molecular Biology Reports - Alzheimer's disease is a common neurodegenerative disease in the elderly population and a leading cause of dementia. Genetics and environmental risk factors were...     

Ariopsis macrosperma sp. nov. (Araceae) from the northern Western Ghats,India

Ariopsis macrosperma sp. nov. from Western Ghats of Maharashtra, India, is described and illustrated. It differs from the other two species in the genus, A. peltata and A. protanthera, in having a typical terrestrial habit, growing on the soil as undergrowth below the forest canopy, thick, leathery leaves and lower number of larger, ovoid and ribbed seeds.     

Delivery systems for gene therapy

The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy.     

Corneal Transplantation in Disease Affecting Only One Eye: Does It Make a Difference to Habitual Binocular Viewing?

Background

Clarity of the transplanted tissue and restoration of visual acuity are the two primary metrics for evaluating the success of corneal transplantation. Participation of the transplanted eye in habitual binocular viewing is seldom evaluated post-operatively. In unilateral corneal disease, the transplanted eye may remain functionally inactive during binocular viewing due to its suboptimal visual acuity and poor image quality, vis-à-vis the healthy fellow eye.

Methods and Findings

This study prospectively quantified the contribution of the transplanted eye towards habitual binocular viewing in 25 cases with unilateral transplants [40yrs (IQR: 32–42yrs) and 25 age-matched controls [30yrs (25–37yrs)]. Binocular functions including visual field extent, high-contrast logMAR acuity, suppression threshold and stereoacuity were assessed using standard psychophysical paradigms. Optical quality of all eyes was determined from wavefront aberrometry measurements.Binocular visual field expanded by a median 21% (IQR: 18–29%) compared to the monocular field of cases and controls (p = 0.63). Binocular logMAR acuity [0.0 (0.0–0.0)] almost always followed the fellow eye’s acuity [0.00 (0.00 –-0.02)] (r = 0.82), independent of the transplanted eye’s acuity [0.34 (0.2–0.5)] (r = 0.04). Suppression threshold and stereoacuity were poorer in cases [30.1% (13.5–44.3%); 620.8arc sec (370.3–988.2arc sec)] than in controls [79% (63.5–100%); 16.3arc sec (10.6–25.5arc sec)] (p<0.001). Higher-order wavefront aberrations of the transplanted eye [0.34μ (0.21–0.51μ)] were higher than the fellow eye [0.07μ (0.05–0.11μ)] (p<0.001) and their reduction with RGP contact lenses [0.09μ (0.08–0.12μ)] significantly improved the suppression threshold [65% (50–72%)] and stereoacuity [56.6arc sec (47.7–181.6arc sec)] (p<0.001).

Conclusions

In unilateral corneal disease, the transplanted eye does participate in gross binocular viewing but offers limited support to fine levels of binocularity. Improvement in the transplanted eye’s optics enhances its participation in binocular viewing. Current metrics of this treatment success can expand to include measures of binocularity to assess the functional benefit of the transplantation process in unilateral corneal disease.     

Uncialamycin as a novel payload for antibody drug conjugate (ADC) based targeted cancer therapy

Uncialamycin analogs were evaluated as potential cytotoxic agents in an antibody-drug conjugate (ADC) approach to treating human cancer. These analogs were synthesized using Hauser annulations of substituted phthalides as a key step. A highly potent uncialamycin analog 3c with a valine-citrulline dipeptide linker was conjugated to an anti-mesothelin monoclonal antibody (mAb) through lysines to generate a meso-13 conjugate. This conjugate demonstrated subnanomolar potency (IC50?=?0.88?nM, H226 cell line) in in vitro cytotoxicity experiments with good immunological specificity to mesothelin-positive lung cancer cell lines. The potency and mechanism of action of this uncialamycin class of enediyne antitumor antibiotics make them attractive payloads in ADC-based cancer therapy.     

Synthesis and biological screening of a combinatorial library of β-chlorovinyl chalcones as anticancer,anti-inflammatory and antimicrobial agents

A combinatorial library of β-chlorovinyl chalcones (4) were synthesized by Claisen–Schmidt condensation reaction. Catalytic reaction of substituted 3-chloro-3-phenyl-propenal (2) and 1-(2,4-dimethoxy-phenyl)-ethanone or 1-(4-methoxy-phenyl)-ethanone (3) in alkaline conditions furnished the target compound 5-chloro-1-(2,4-dimethoxy-phenyl)-5-phenyl-penta-2,4-dien-1-one (4). The synthesized compounds were screened for their biological activity viz. anticancer, anti-inflammatory and antimicrobial activities. Synthesized compounds 4g and 4h revealed promising anti-inflammatory activity (66–67% TNF-α and 95–97% IL-6 inhibitory activity at 10 μM). Cytotoxicity of the compounds checked using CCK-8 cell lines and found to be nontoxic to slightly toxic. Furthermore, the anticancer activity (30–40%) was shown by compounds 4d, 4e, 4h and 4b at 10 μM concentrations against ACHN followed by Calu 1, Panc1, HCT116 and H460 cell lines. Some of the compounds 4d, 4e, 4a, 4i and 4b revealed promising antimicrobial activity at MIC 50–100 μg/mL against selected pathogenic bacteria and fungi.     

Development of Novel Docetaxel Phospholipid Nanoparticles for Intravenous Administration: Quality by Design Approach

The objective of this study was to develop novel docetaxel phospholipid nanoparticles (NDPNs) for intravenous administration. Modified solvent diffusion-evaporation method was adopted in the NDPN preparation. Central composite design (CCD) was employed in the optimization of the critical formulation factor (drug content) and process variable (stirring rate) to obtain NDPNs with 215.53 ± 1.9-nm particle size, 0.329 ± 0.02 polydispersity index (PDI), and 75.41 ± 4.81% entrapment efficiency. The morphological examination by transmission electron microscopy revealed spherical structure composed of a drug core stabilized within the phospholipid shell. Enhanced cell uptake of coumarin-6-loaded phospholipid nanoparticles by MCF-7 cell line indicated NDPN-efficient cell uptake. In vitro hemolysis test confirmed the safety of the phospholipid nanoparticles. NDPNs exhibited increased area under the curve (AUC) and mean residence time (MRT) by 3.0- and 3.3-fold, respectively, in comparison with the existing docetaxel parenteral formulation (Taxotere®), indicating a potential for sustained action. Thus, the novel NDPNs exhibit an ability to be an intravenous docetaxel formulation with enhanced uptake, decreased toxicity, and prolonged activity.KEY WORDS: cancer, delivery vehicle, docetaxel phospholipid nanoparticles, nanoparticles, pharmacokinetics     

Complete sequence and organisation of the <Emphasis Type="Italic">Jatropha curcas</Emphasis> (Euphorbiaceae) chloroplast genome

Jatropha curcas is an important non-edible oil seed tree species and is considered a promising source of biodiesel. The complete nucleotide sequence of J. curcas chloroplast genome (cpDNA) was determined by pyrosequencing and gaps filled by Sanger sequencing. The cpDNA is a circular molecule of 163,856 bp in length and codes for 110 distinct genes (78 protein coding, four rRNA and 28 distinct tRNA). Genome organisation and arrangement are similar to the reported angiosperm chloroplast genome. However, in Jatropha, the infA and the rps16 genes are non-functional. The inverted repeat (IR) boundary is within the rpl2 gene, and the 13 nucleotides at the ends of the two duplicate genes are different. Repeat analysis suggests the presence of 72 repeat regions (>30 bp) apart from the IR; of these, 48 were direct and 24 were palindromic repeats. Phylogenetic analysis of 81 protein coding chloroplast genes from 65 taxa by maximum parsimony, maximum likelihood and minimum evolution analyses at 100 bootstraps provide strong support for the placement of inaperturate crotonoids of which Jatropha is a member as sister to articulated crotonoids of which Manihot is a member.